Quaas Alexander, Rahvar Amir-Hossein, Burdelski Christoph, Koop Christina, Eichelberg Christian, Rink Michael, Dahlem Roland, Schlomm Thorsten, Tsourlakis Maria Christina, Simon Ronald, Minner Sarah, Sauter Guido, Steurer Stefan
Department of Pathology, Institute of Pathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany.
Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
World J Urol. 2015 Oct;33(10):1561-9. doi: 10.1007/s00345-014-1463-6. Epub 2014 Dec 21.
βIII-tubulin (TUBB3) is a microtubule component overexpression of which is found in many solid cancer types, often linked to poor patient prognosis, and has been suggested to predict failure of microtubule-targeting chemotherapeutics. This study was designed to determine prevalence and prognostic impact of TUBB3 expression in kidney cancers.
A tissue microarray (TMA) containing more than 1,200 renal tumors was analyzed by immunohistochemistry. TUBB3 expression varied markedly between the different histological subtypes and was more frequent in 105 papillary cancers (75.2 %, p < 0.0001), 38 oncocytomas (52.6 %, p < 0.0001), and 22 chromophobic carcinomas (36.4 %, p = 0.1221) than in 555 clear cell RCC (16.4 %). In clear cell cancers, strong TUBB3 positivity was linked to high Fuhrman grade (p < 0.0001), advanced stage (0.002), nodal metastases (p = 0.0433), hematogenous metastases (p = 0.0016), and shortened overall survival (p < 0.0001). Associations with outcome and tumor phenotype were inversely for papillary RCC, where TUBB3 immunostaining was linked to low tumor stage (p = 0.0012) and prolonged survival (p = 0.0043).
TUBB3 expression levels and their effects are strikingly different between ccRCC and papillary RCC. These differences may be caused by differences in VHL function between these RCC subtypes, because VHL (like TUBB3) is another strong regulator of microtubule function.
βIII-微管蛋白（TUBB3）是一种微管成分，在许多实体癌类型中均有过表达，这通常与患者预后不良相关，并且有人提出它可预测微管靶向化疗药物的疗效不佳。本研究旨在确定TUBB3表达在肾癌中的发生率及其预后影响。
通过免疫组织化学分析了一个包含1200多个肾肿瘤的组织微阵列（TMA）。TUBB3表达在不同组织学亚型之间差异显著，在105例乳头状癌（75.2%，p<0.0001）、38例嗜酸细胞瘤（52.6%，p<0.0001）和22例嫌色细胞癌（36.4%，p = 0.1221）中比在555例透明细胞肾细胞癌（RCC）（16.4%）中更常见。在透明细胞癌中，TUBB3强阳性与高Fuhrman分级（p<0.0001）、晚期（0.002）、淋巴结转移（p = 0.0433）、血行转移（p = 0.0016）以及总生存期缩短（p<0.0001）相关。对于乳头状RCC，TUBB3免疫染色与低肿瘤分期（p = 0.0012）和生存期延长（p = 0.0043）呈负相关，这与结局和肿瘤表型的相关性相反。
透明细胞RCC和乳头状RCC之间TUBB3表达水平及其影响存在显著差异。这些差异可能是由这些RCC亚型之间VHL功能的差异引起的，因为VHL（与TUBB3一样）是微管功能的另一个重要调节因子。
